The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

The combination of
cobimetinib with vemurafenib improves progression-free survival compared with
placebo and vemurafenib in previously untreated patients with BRAFV600-mutant
advanced melanoma, as previously reported in the coBRIM study. In this Article,
we report updated efficacy results, including overall survival and safety after
longer follow-up, and selected biomarker correlative studies. In this double-blind,
randomised, placebo-controlled, multicentre study, adult patients (aged ≥18
years) with histologically confirmed BRAFV600 mutation-positive unresectable
stage IIIC or stage IV melanoma were randomly assigned (1:1) using an
interactive response system to receive cobimetinib (60 mg once daily for 21
days followed by a 7-day rest period in each 28-day cycle) or placebo, in
combination with oral vemurafenib (960 mg twice daily). Progression-free and
overall survival were primary and secondary endpoints, respectively; all
analyses were done on the intention-to-treat population. This study is
registered with ClinicalTrials.gov, number NCT01689519, and is ongoing but no
longer recruiting participants. Between Jan 8, 2013, and Jan
31, 2014, 495 eligible adult patients were enrolled and randomly assigned to
the cobimetinib plus vemurafenib group (n=247) or placebo plus vemurafenib
group (n=248). At a median follow-up of 14·2 months, the updated
investigator-assessed median progression-free survival was 12·3 months for
cobimetinib and vemurafenib versus 7·2 months for placebo and vemurafenib. The
final analysis for overall survival occurred when 255 (52%) patients had died
(Aug 28, 2015). Median overall survival was 22·3 months for cobimetinib and
vemurafenib versus 17·4 months for placebo and vemurafenib. The safety profile
for cobimetinib and vemurafenib was tolerable and manageable, and no new safety
signals were observed with longer follow-up. The most common grade 3-4 adverse
events occurring at a higher frequency in patients in the cobimetinib and
vemurafenib group compared with the vemurafenib group were γ-glutamyl
transferase increase (36 [15%] in the cobimetinib and vemurafenib group vs 25
[10%] in the placebo and vemurafenib group), blood creatine phosphokinase
increase (30 [12%] vs one [less than 1%]), and alanine transaminase increase
(28 [11%] vs 15 [6%]). Serious adverse events occurred in 92 patients (37%) in
the cobimetinib and vemurafenib group and 69 patients (28%) in the vemurafenib
group. Pyrexia (six patients [2%]) and dehydration (five patients [2%]) were
the most common serious adverse events reported in the cobimetinib and
vemurafenib group. A total of 259 patients have died: 117 (47%) in the
cobimetinib and vemurafenib group and 142 (58%) in the vemurafenib group. The
primary cause of death was disease progression in most patients: 109 (93%) of
117 in the cobimetinib and vemurafenib group and 133 (94%) of 142 in the
vemurafenib group. These data confirm the
clinical benefit of cobimetinib combined with vemurafenib and support the use
of the combination as a standard first-line approach to improve survival in
patients with advanced BRAFV600-mutant melanoma.

And as one would assume....progression free survival as well as median overall survival was greater when vemurafenib was combined with cobimetinib than when it was given with a placebo. Perhaps a little surprising was the fact that side effects were higher in those receiving the cobimetinib and vemurafenib combo, as the BRAFi/MEKi combo's are generally shown to have greater efficacy than BRAFi given alone, but also produce FEWER side effects in previous studies.